The major macromolecular component of monkey cervical mucus has been purified from crude monkey cervical mucus at various times during a hormonally induced estrous cycle. The major component, a high-molecular weight glycoprotein, was secreted in large amounts in midcycle mucus. The glycoprotein exhibited human blood group B activity and contained the same concentration of L-fucose, D-galactose, N-acetyl-D-galactosamine, and N-acetyl-D-glucosamine during the cycle. There were no changes in the amino acid composition or in the number of carbohydrate side chains. There was a significant increase in the amount of sialic acid in the glycoprotein purified from midcycle mucus. Changes in the specific viscosity and the far ultraviolet circular dichroic spectra were also observed. The possible control of sperm penetration by the glycoprotein is discussed.